Bond David J, Andreazza Ana C, Hughes John, Dhanoa Taj, Torres Ivan J, Kozicky Jan-Marie, Young L Trevor, Lam Raymond W, Yatham Lakshmi N
Mood Disorders Centre, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 2A1, Canada; Department of Psychiatry, University of Minnesota, 2450 Riverside Avenue, Minneapolis, MN 55454, USA.
Departments of Psychiatry and Pharmacology, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada.
Psychoneuroendocrinology. 2016 Mar;65:76-83. doi: 10.1016/j.psyneuen.2015.12.012. Epub 2015 Dec 18.
Bipolar I disorder (BD) is associated with increased inflammation, which is believed to be central to disease etiology and progression. However, BD patients also have high rates of obesity, itself an inflammatory condition, and the relative contributions of mood illness and obesity to inflammation are unknown. Moreover, the impact of inflammation on clinical illness course has not been well studied. The objectives of this analysis were therefore: (1) to determine if inflammation in BD is mood illness-related or secondary to elevated body mass index (BMI), and (2) to investigate the impact of inflammation on prospectively-ascertained relapse into depression and mania. We measured the serum levels of 7 inflammatory cytokines (TNF-α, γ-interferon, monocyte chemoattractant protein-1 [MCP-1], IL-1α, IL-2, IL-6, and IL-8) and 2 anti-inflammatory cytokines (IL-4 and IL-10) in 52 early-stage BD patients and 22 healthy subjects. In patients, a multivariate multiple regression model that controlled for psychotropic medications found that higher BMI, but not recent (past-6-month) mood episodes, predicted greater inflammatory cytokines (p=.05). Healthy subjects also had a BMI-related increase in inflammatory cytokines (p<.01), but it was counter-balanced by a compensatory increase in anti-inflammatory cytokines (p=.02), reducing their total inflammatory burden from higher BMI. In patients, linear regression showed that two inflammatory cytokines predicted depressive relapse in the 12 months after cytokine measurement: IL-1α (p<.01) and MCP-1 (p<.01). These results suggest that elevated BMI is a significant contributor to inflammation in BD, more so even than recent mood illness severity. They also point to inflammation as an important predictor of illness course, particularly depressive relapse.
双相 I 型障碍（BD）与炎症增加有关，炎症被认为是疾病病因和进展的核心。然而，BD 患者肥胖率也很高，而肥胖本身就是一种炎症状态，情绪疾病和肥胖对炎症的相对影响尚不清楚。此外，炎症对临床病程的影响尚未得到充分研究。因此，本分析的目的是：（1）确定 BD 中的炎症是与情绪疾病相关还是继发于体重指数（BMI）升高，以及（2）研究炎症对前瞻性确定的抑郁和躁狂复发的影响。我们测量了 52 例早期 BD 患者和 22 例健康受试者血清中 7 种炎性细胞因子（肿瘤坏死因子-α、γ-干扰素、单核细胞趋化蛋白-1 [MCP-1]、白细胞介素-1α、白细胞介素-2、白细胞介素-6 和白细胞介素-8）和 2 种抗炎细胞因子（白细胞介素-4 和白细胞介素-10）的水平。在患者中，一个控制了精神药物的多元多重回归模型发现，较高的 BMI，而非近期（过去 6 个月）的情绪发作，可预测更高水平的炎性细胞因子（p = 0.05）。健康受试者的炎性细胞因子也随 BMI 升高而增加（p < 0.01），但被抗炎细胞因子的代偿性增加所抵消（p = 0.02），从而减轻了因较高 BMI 导致的总炎症负担。在患者中，线性回归显示，两种炎性细胞因子可预测细胞因子测量后 12 个月内的抑郁复发：白细胞介素-1α（p < 0.01）和 MCP-1（p < 0.01）。这些结果表明，BMI 升高是 BD 炎症的一个重要促成因素，甚至比近期情绪疾病的严重程度更甚。它们还指出炎症是疾病病程的一个重要预测指标，尤其是抑郁复发。
